Treating metastatic central nervous system (CNS) tumors

Let’s look at how to treat metastatic central nervous system (CNS) tumors. We will discuss commonly used medications, and then treatment options involving surgery and radiation (which can vary depending on the circumstances).

Seizures are very common in patients with cerebral metastases and can significantly complicate patient management. In cases of brain metastasis, start anticonvulsant therapy regardless of whether the patient has a prior history of seizures.

Levetiracetam at 500–1 000 mg twice a day is currently a popular approach. Phenytoin at 100 mg three times a day is another approach that has been utilized for decades.

If the patient is symptomatic, or they have significant edema and mass effect associated with a lesion on imaging, initiate 4–6 mg dexamethasone every 6 hours. Symptoms of brain metastases may include headache, nausea, vomiting, neurological deficits, or seizures. This regimen should be implemented before definitive treatment and will usually be tapered off after the treatment.

Metastases are often accompanied by significant brain swelling (i.e., edema). This can cause neurological deficits, and signs of increased intracranial pressure such as headaches, nausea, vomiting, and lethargy. Corticosteroids are remarkably efficient at reducing edema and the related symptoms, although this improvement manifests more clinically than on imaging.

Corticosteroids are also felt to be neuroprotective when given before an insult (such as surgery). Patients with newly diagnosed metastases, particularly those who are symptomatic, often benefit from initiating medications such as dexamethasone. Remember, a medication like dexamethasone can upset glucose regulation, cause gastrointestinal bleeding, increase the risk of infection, and suppress the adrenal gland, so use it judiciously.

Consult oncology services to assess both the primary cancer and any other metastatic lesions. In patients with brain metastases, it is common to discover metastases in the lungs, liver, and / or bones.

Consult neurosurgery about surgical removal and / or stereotactic radiation of the brain lesions. If the source of the metastasis is identified elsewhere in the body, oncology should take over the patient's overall care to treat and follow the primary disease.

Oncology should be involved in the patient’s care from the beginning, even if they are first headed to brain surgery. If a brain tumor proves to be a metastasis after surgery, oncology will be consulted regardless.

If the definitive disease is noted elsewhere in the body, consider an extracranial biopsy and staging before proceeding with an invasive cerebral procedure. Generally, such procedures carry a low-risk profile.

Evolving approaches to treating metastatic tumors of the brain

Traditionally, patients with brain metastases used to undergo whole-brain radiation even if one or more brain lesions were first removed surgically. The concept was to try to catch micrometastases (e.g., those present but not seen on imaging) before they grew big enough to cause problems.

Unfortunately, whole-brain radiation is not risk-free and may contribute to cognitive loss over time, particularly in patients who survive more than a year. Efforts are currently underway to limit radiation to the whole brain and focus on only addressing definitive lesions.

Management recommendations for cerebral metastases are constantly evolving as more evidence mounts about various approaches. The role of surgery and stereotactic radiation as adjuncts to—or replacing—whole-brain radiation is currently under study and debate. Some clinicians feel that the removal of small numbers of tumors with surgery or stereotactic radiation followed by monitoring for new metastases may help to preserve cognitive function, as opposed to subjecting the entire brain to radiation.

Treating metastatic lesions with unconfirmed primary disease

If there is a single lesion, and no confirmed primary disease, consult neurosurgery for resection of the solitary lesion (excisional biopsy) or stereotactic needle biopsy (if resection carries too much risk). The biopsy results will then inform your treatment protocol. The current trend is to irradiate the tumor or the tumor bed after biopsy with stereotactic radiation (and forgo whole-brain radiation).

If there are many lesions, and no confirmed primary disease, consult neurosurgery for biopsy of an accessible lesion. Further treatment will be determined from the biopsy results.

Treating metastatic lesions with uncontrollable primary disease

If the primary disease is uncontrollable, and there is a short life expectancy, consider whole-brain radiation without surgery and discuss expectant care with your patient. Expectant care means supportive care in the expectation that the patient will soon die and could involve hospice and end-of-life or palliative care specialists.

A single metastatic lesion with a stable primary disease

If the patient has a stable and known cancer, with no signs of imminent demise and a solitary metastasis, consult neurosurgery and radiation oncology for a lesion excision followed by stereotactic radiation to the tumor bed. Follow-up whole-brain radiation may or may not be recommended to eliminate other micrometastases.

Multiple metastases

In recent years, the biggest debate surrounding metastatic brain tumors involves the management of multiple identified metastases (particularly five or fewer lesions). As a result, the following recommendations are constantly evolving.

Multiple metastases with one large lesion

If the patient has a stable systemic disease with multiple metastases and one of the lesions is large and causing significant mass effect, consider surgical resection of the larger lesion followed by radiation treatment to the other lesions. The goal is to help control the mass effect from the larger lesion.

Multiple metastases with less than five accessible lesions

If there are fewer than five accessible lesions (although this number is under great debate), consult neurosurgery for resection of the lesions followed by stereotactic radiation and / or whole-brain radiation. Neurosurgery must be confident that they can safely remove all visible lesions if they are to proceed with surgery. If the lesions are not candidates for surgical resection and are few in number, stereotactic radiation can be considered for each lesion.

Multiple metastases with five or more accessible lesions

If there are five or more lesions, consult radiation oncology to consider stereotactic radiation to each individual lesion, or whole-brain radiation. Surgery is not currently recommended unless one or two of the tumors are particularly large and are causing significant edema and mass effect.

Multiple metastases with innumerable lesions

If there are innumerable lesions, consult radiation oncology for whole-brain radiation. Stereotactic radiation and surgical resection are not currently indicated for metastatic lesions that are innumerable.

Keep in mind that surgical resection is generally not recommended for metastases stemming from highly radiation-sensitive primary tumors. This includes small cell carcinoma of the lung, germ cell tumors, lymphoma, and multiple myeloma. Also, metastatic tumors are rarely treated with surgery alone. Once a tumor is resected, it will almost always be followed with some form of radiation treatment (stereotactic or whole brain).

Follow-up radiation treatment is always indicated since the microscopic disease will persist in the region of the tumor bed. Metastatic recurrence usually occurs at the sight of the previous resection unless the area received adjuvant radiation treatment.

Metastases in the spine occur in 10% of all cancer patients and are often found in multiples. The thoracic spine is affected more frequently than the rest of the spine. Suspect spinal metastases in a cancer patient with severe spinal pain, particularly if the pain persists when the patient is lying down or if the pain wakes the patient up.

Aggressive surgical resection of spinal metastases followed by radiation may offer some modest improvement in survival time. However, surgeries for spinal metastases can be large, morbid surgeries and should not be considered in patients with extensive primary disease or multiple spinal lesions. Surgery is always followed by radiation treatment to the area (whole-brain or stereotactic).

Metastatic spinal lesions with a rapid decline in neurological function

If a patient with metastatic spinal lesions shows a rapid decline in function, and imaging demonstrates significant spinal cord compression, consult neurosurgery for emergent decompression to be followed later by radiation treatment. Decompressive surgery, if enacted immediately, can sometimes reverse severe acute neurological deficits.

In a patient with a rapid decline in neurological function, start dexamethasone therapy at the usual dosage of 6–10 mg every 6 hours.

Metastatic spinal lesions with vertebral fracture

If a patient has sustained a significant pathological fracture (with or without neurological compromise), consult neurosurgery to consider decompression and instrumentation of the affected area followed by radiation treatment.

Metastatic spinal lesion with no neurological decline or spinal instability

If a metastatic tumor is discovered, but the patient demonstrates no significant neurological compromise or spinal instability, consult radiation oncology for radiation of the affected area. This type of presentation will be the majority of your metastatic spinal lesion cases.

Generally, surgery will not be undertaken unless the oncology team feels that it will contribute to the patient’s overall survival. Otherwise, treatment will include radiation to the affected region and treatment of the systemic disease (if feasible).

Metastatic spinal lesions with ongoing total paralysis

If a patient with a metastatic lesion presents with total paralysis for more than 24 hours, the odds of a return of meaningful function through surgery approaches zero. Move to radiation oncology consultation.

Metastatic lesions with progressive paralysis and residual motor function

Patients with progressive paralysis, but some residual motor function, should be considered for emergent surgery. Surgery is not indicated for patients with a projected survival of fewer than four months, poor medical conditions, or highly radiation-sensitive tumors.

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